Fig. 16-1

The Molecular Basis of

Inheritance

Chapter 16: The Molecular

Basis of Inheritance

Additional Evidence That DNA Is the Genetic Material

• It was known that DNA is a polymer of

nucleotides, each consisting of a nitrogenous

base, a sugar, and a phosphate group

• In 1950, Erwin Chargaff reported that DNA

composition varies from one species to the

next

• This evidence of diversity made DNA a more

credible candidate for the genetic material

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Animation: DNA and RNA Structure

• Chargaff’s rule states that in any species

there is an equal number of A and T bases,

and an equal number of G and C bases

• Knowing what we already know about DNA

structure, why do you think that this rule would

be valid?

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Building a Structural Model of DNA: Scientific Inquiry

• Maurice Wilkins and Rosalind Franklin were using a

technique called X-ray crystallography to study

molecular structure

• Franklin produced a picture of the DNA molecule

using this technique

(a) Rosalind Franklin (b) Franklin’s X-ray diffraction

photograph of DNA

• Franklin’s X-ray crystallographic images of

DNA enabled Watson to deduce that DNA was

helical

• The X-ray images also enabled Watson to

deduce the width of the helix and the spacing

of the nitrogenous bases

• The width suggested that the DNA molecule

was made up of two strands, forming a double

helix

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Animation: DNA Double Helix

Fig. 16-7

(c) Space-filling model

Hydrogen bond 3 end

5 end

3.4 nm

0.34 nm

3 end

5 end

(b) Partial chemical structure (a) Key features of DNA structure

1 nm

• Watson and Crick built models of a double helix

to conform to the X-rays and chemistry of DNA

• Franklin had concluded that there were two

antiparallel sugar-phosphate backbones, with

the nitrogenous bases paired in the molecule’s

interior - (this means two separate strands

made up of A, G, C and T).

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Purine + purine: too wide

Pyrimidine + pyrimidine: too narrow

Purine + pyrimidine: width consistent with X-ray data

At first, Watson and Crick thought the bases paired like with like (A with A, and so on), but such pairings did not result in a uniform width Instead, pairing a purine with a pyrimidine resulted in a uniform width consistent with the X-ray

• Watson and Crick reasoned that the pairing

was more specific, dictated by the base

structures

• They determined that adenine (A) paired only

with thymine (T), and guanine (G) paired only

with cytosine (C)

• The Watson-Crick model explains

Chargaff’s rules: in any organism the

amount of A = T, and the amount of G = C

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Fig. 16-8

Cytosine (C)

Adenine (A) Thymine (T)

Guanine (G)

Fig. 16-9-3

A T

G C

T A

T A

G C

(a) Parent molecule

A T

G C

T A

T A

G C

(c) “Daughter” DNA molecules, each consisting of one parental strand and one new strand

(b) Separation of

strands

A T

G C

T A

T A

G C

A T

G C

T A

T A

G C

Getting Started

• Replication begins at special sites called

origins of replication (meaning where

replication starts), where the two DNA strands

are separated, opening up a replication

“bubble”

• A eukaryotic chromosome may have hundreds

or even thousands of origins of replication

• Replication proceeds in both directions from

each origin, until the entire molecule is copied

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Animation: Origins of Replication

Fig. 16-12 Origin of replication Parental (template) strand

Daughter (new) strand

Replication fork

Replication bubble

Two daughter DNA molecules

(a) Origins of replication in E. coli

Origin of replication Double-stranded DNA molecule

Parental (template) strand Daughter (new) strand

Bubble Replication fork

Two daughter DNA molecules

(b) Origins of replication in eukaryotes

0.5 µm

0.25 µm

Double- stranded DNA molecule

Fig. 16-13

Topoisomerase

Helicase

Primase Single-strand binding

proteins

RNA

primer

5 5

5 3

3

3

Synthesizing a New DNA Strand

• Enzymes called DNA polymerases catalyze

the elongation of new DNA at a replication fork

• Most DNA polymerases require a primer and a

DNA template strand

• The rate of elongation is about 500 nucleotides

per second in bacteria and 50 per second in

human cells

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Antiparallel Elongation

• The antiparallel structure of the double helix

(two strands oriented in opposite directions)

affects replication

• DNA polymerases add nucleotides only to the

free 3end of a growing strand

• Along one template strand of DNA, the DNA

polymerase synthesizes a leading strand

continuously, moving toward the replication

fork

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Animation: Leading Strand

Fig. 16-15a

Overview

Leading strand

Leading strand Lagging strand

Lagging strand

Origin of replication

Primer

Overall directions

of replication

Fig. 16-15b

Origin of replication

RNA primer

“Sliding clamp”

DNA pol III Parental DNA

3

5

5

5

5

5

5

3

3

3

• To elongate the other new strand, called the

lagging strand, DNA polymerase must work in

the direction away from the replication fork

• The lagging strand is synthesized as a series of

segments called Okazaki fragments, which

are joined together by DNA ligase

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Animation: Lagging Strand

Fig. 16-16 Overview

Origin of replication

Leading strand

Leading strand

Lagging strand

Lagging strand

Overall directions of replication

Template strand

RNA primer

Okazaki fragment

Overall direction of replication

1 2

3

2

1

1

1

1

2

2

5

1 3

3

3

3

3

3

3

3

3

5

5

5

5

5

5

5

5

5

5

5 3

3

Proofreading and Repairing DNA

• DNA polymerases proofread

newly made DNA, replacing

any incorrect nucleotides

• In mismatch repair of DNA,

repair enzymes correct errors

in base pairing

• In nucleotide excision

repair, a nuclease cuts out

and replaces damaged

stretches of DNA

Nuclease

DNA polymerase

DNA ligase